The present invention relates generally to cardiac therapeutic devices, and specifically to cardiac pacemakers.
The heart is a muscular pump whose mechanical activation is controlled by electrical stimulation generated at the right atrium and passed to the entire heart. In a normal heart the electrical stimulation originates as action potentials in a group of pacemaker cells lying in a sino-atrial (SA) node in the right atrium. In certain heart diseases, either congenital or acquired, natural pacing is replaced or assisted by artificial pacing induced by an implanted pacemaker. Pacemakers known in the art provide artificial excitatory pulses to the heart tissue, to control the heart rhythm.
Cardiac output, i.e., the output of the heart per unit time, is the product of stroke volume and heart rate. Hence, variations in cardiac output can be produced by changes in cardiac rate or stroke volume. The stroke volume can be influenced, for example, by changing the efficacy of cardiac contraction, by changing the length of the cardiac muscle fibers, and by changing contractility of cardiac muscle independent of fiber length. The heart rate and rhythm influence the cardiac output both directly and indirectly, since changes in the rate and rhythm also affect myocardial contractility.
The human body normally regulates the cardiac output in response to physiological needs, mainly by changing the heart rate, as during physical exercise, and/or by adapting the stroke volume. Under pathological conditions, however, some of the regulatory mechanisms may be damaged.
Artificially paced hearts typically lose more than 30% of their normal cardiac output, presumably due to loss of efficient contraction under artificial, as opposed to natural, electrical stimulation. In the context of the present patent application, this reduction is referred to as pacing-induced cardiac output (PICO) loss.
Moreover, when pacing is indicated, it is frequently in the wake of heart disease, particularly ischemic heart disease (IHD), including cases of myocardial infarction (MI), which in itself reduces the cardiac output. Such reduction is referred to in the context of the present patent application as global cardiac output (GCO) loss.
While electronic pacemakers can increases cardiac output temporarily by increasing the heart rate, this increase is at the expense of greater energy expenditure by the heart muscle, which the heart disease patient cannot generally sustain. Although modern pacemakers may include stimulation at two or more points and allow optimization of the excitatory pulse amplitudes, rate and timing, they do not address directly the loss of cardiac output caused by the pacing, nor do they address the loss due to cardiac pathology. These losses are mainly related to reduction in the stroke volume, which cardiac pacing tends to exacerbate. Defibrillators are useful in treating arrhythmia when it occurs (although they are painful to the patient and traumatic to the heart), but they provide no long-term amelioration of cardiac insufficiency. Thus, none of the treatments known in the art allow effective, long-term regulation of cardiac output, because they are aimed at controlling the heart rate and do not address the need to increase the stroke volume and the efficiency of contraction of the heart.
The electromechanical properties of the heart, as well as methods known in the art for influencing these properties, are more fully described in the xe2x80x9cBackground of the Inventionxe2x80x9d section of PCT patent application PCT/IL97/00012, which is assigned to the assignee of the present patent application, and whose disclosure is incorporated herein by reference.
The inventors have found that by applying non-excitatory electrical stimulation pulses to cardiac muscle segments, appropriately timed with respects the heart""s electrical activation, it is possible to regulate the cardiac output.
It is therefore an object of the present invention to provide devices that allow both artificial heart pacing and effective regulation of cardiac output, and particularly devices that increase the cardiac output by enhancing the heart""s stroke volume.
The present invention thus provides thus provides apparatus for heart pacing with cardiac output regulation, including one or more implantable electrodes, which apply electrical signals to cardiac muscle segments, and signal generation circuitry, which applies an excitatory electrical pulse to at least one of the one or more electrodes to pace the heart and a non-excitatory stimulation pulse to at least one of the one or more electrodes to regulate the cardiac output.
Another aspect of the present invention relates to a method for heart pacing with cardiac output enhancement, including implanting one or more electrodes in a subject""s heart; applying an excitatory electrical pulse to at least one of the one or more electrodes to pace the heart; and applying a non-excitatory stimulation pulse to at least one of the one or more electrodes to regulate an efficacy of cardiac contraction.
The term xe2x80x9cnon-excitatory electrical stimulationxe2x80x9d, in the context of the present patent application and in the claims, refers to electrical pulses that do not induce new activation potentials to propagate in cardiac muscle cells. Rather, such pulses affect the response of the heart muscle to the action potentials, by modulating cell contractility within selected segments of the cardiac muscle. Specifically, as described in the above-mentioned PCT patent application PCT/IL97/00012 and incorporated herein by reference, the inventors have found that by applying non-excitatory electrical stimulation pulses of suitable strength, appropriately timed with respect to the heart""s electrical activation, the contraction of the selected segments can be increased or decreased, thus increasing or decreasing the stroke volume of the heart. This finding forms the basis for the present invention.
According to preferred embodiments of the present invention, the non-excitatory stimulation pulse is coupled to the activity of a pacemaker, and in various embodiments, the non-excitatory stimulation pulse is synchronized by pacing pulses generated by the pacemaker. In other embodiments of the present invention, one or more sensors are provided in the apparatus to sense local activity in the heart tissue, to enable the non-excitatory stimulation pulse to be triggered independently of the pacemaker, particularly when the pacemaker is inactive for a period of time, as is known in the art, for example, with regard to VVI and DDD pacemakers.
In preferred embodiments of the present invention, a cardiac output enhanced pacemaker (COEP) comprises a pacing unit and a non-excitatory stimulation unit. The pacing unit provides pacing pulses to the heart muscle for controlling the heart rate, as is known in the art. The non-excitatory stimulation unit provides stimulation pulses to at least a segment of the heart muscle, synchronized with the pacing pulses, so as to enhance the response of the muscle to the pacing pulses, preferably to increase the heart""s stroke volume. Each of the two units comprises one or more electrodes to be implanted in a subject""s heart and signal generation circuitry coupled thereto. The circuitry is preferably encased in an implantable case, similar to those used in pacemakers known in the art, and preferably uses a similar type of battery as a power source.
Thus, in preferred embodiments of the present invention, the COEP device applies both excitatory electrical stimulation, to pace the heart by generating activation potentials in the cardiac muscle tissue, a non-excitatory stimulation, to control response of the muscle to the activation potentials. In this respect, the device differs fundamentally from pacemakers and other implantable cardiac electronic devices known in the art, which provide only excitatory stimulation. When the COEP is used to pace the heart, the activation of the heart with respect to the pacing is substantially the same as it would be if an ordinary pacemaker were used. By applying non-excitatory stimulation to the heart, however, the COEP allows cardiac output to be regulated to demand by controlling the stroke volume, as well as the heart rate. It is preferably used to compensate for the loss of cardiac output that commonly results from the pacing, and may also be used to treat problems of low cardiac output due to other cardiac pathologies.
Preferably, the COEP device can be controlled to apply both excitatory and non-excitatory stimulation together, or to apply either excitatory or non-excitatory stimulation alone, depending on the therapeutic needs and condition of the patient. Thus, for example, the excitatory stimulation could be applied at substantially all hours of the day and night, while the non-excitatory stimulation is applied only during daytime hours, when the patient needs a boost in cardiac output, or at any other desired times. Parameters of the excitatory and non-excitatory stimulation are preferably adjusted together, so as to cooperatively achieve a desired therapeutic effect.
Although in describing some aspects of the present invention, the pacing and non-excitatory stimulation units are, for clarity of explanation, referred to as separate entities, in some preferred embodiments of the present invention, these units are implemented using a common, preferably integrated, electronic circuitry. Similarly, in some preferred embodiments of the present invention, the same electrodes may be used to apply both the pacing and non-excitatory stimulation pulses. Furthermore, while preferred embodiments of the present invention are described herein with reference to the COEP device, certain aspects of the present invention may be accomplished by suitably modifying and/or reprogramming an existing pacemaker, so as to apply non-excitatory stimulation pulses in addition to the pacing pulses that the pacemaker normally generates. It will be appreciated that such embodiments and modifications fall within the scope of the present invention.
In some preferred embodiments of the present invention the pacing unit comprises multiple pacing electrodes to allow for pacing optimization, as is known in the art. More generally, it will be understood that the principles of the present invention may be applied to produce COEP devices that apply non-excitatory stimulation to achieve cardiac output regulation in conjunction with any suitable mode of pacing, including adaptive and rate-responsive pacing modes known in the art.
In preferred embodiments of the present invention, the non-excitatory stimulation unit comprises electrodes having a relatively large contact area with the heart, preferably at least 5 mm2, more preferably at least 1 cm2, most preferably at least 4 cm2, and preferably comprising carbon or another conductive material. Alternatively or additionally, the non-excitatory stimulation unit may comprise a plurality of stimulation electrodes, preferably a stimulation net, comprising a plurality of interconnected, addressable electrodes, covering a substantial heart segment, such that the size of the segment of the heart to which a non-excitatory signal is applied may be modulated. Considerations relating to the design of the electrodes and various preferred embodiments thereof are described in the above-mentioned ""012 PCT application and the PCT patent application filed on even date, entitled xe2x80x9cCardiac Output Controller,xe2x80x9d and incorporated herein by reference.
Although generally the non-excitatory stimulation unit is triggered responsive to the pacing pulses generated by the pacing unit, in some preferred embodiments of the present invention, the COEP comprises one or more sensors, preferably sensing electrodes, which sense local electrical activity in the heart tissue. Alternatively or additionally, one or more of the stimulation electrodes may also serve as sensing electrodes. The signals sensed by the sensing electrodes are received by the circuitry and are used to trigger the non-excitatory stimulation unit and, alternatively or additionally, may be used by the pacing unit in adaptive pacing modes. Additionally, the circuitry may analyze the signals, for example, to determine the QT interval, so as to adjust the stimulation pulses responsive thereto.
Further alternatively, a body surface electrode may be used to detect an ECG signal, which is then used to synchronize the non-excitatory stimulation pulses. Other types of sensors may also be used for this purpose, for example, a pressure sensor or other mechanical sensor in or on the heart, which senses heart muscle activity.
In some preferred embodiments of the present invention, one or more of the pacing electrodes and one or more of the non-excitatory stimulation electrodes are placed in two or more different heart chambers. Preferably, the pacing electrode is implanted in the right ventricle and the non-excitatory stimulation electrode, in the left ventricle. Alternatively, all electrodes may be located in the same chamber of the heart. Further alternatively, one or more of the electrodes may be placed epicardially, on an outer wall of one of the chambers, or may be implanted in the myocardium.
In a preferred embodiment of the present invention, the non-excitatory stimulation electrodes are placed on the heart wall in close proximity to coronary blood vessels. The inventors have found that placing the electrodes in proximity to the blood vessels generally increases the effectiveness of the non-stimulatory excitation pulses in enhancing stroke volume and contraction efficiency.
In some preferred embodiments of the present invention, optimal placement of the electrodes is determined with reference to a map of local cardiac activity and/or viability. Preferably, before insertion of the electrodes, a map of the heart is produced, for example, an electrophysiological map, as described in U.S. Pat. No. 5,568,809, or a phase-dependent geometrical map, as described in PCT Patent Application PCT/IL97/00011, which is assigned to the assignee of the present patent application, both of which documents are incorporated herein by reference. The electrodes are then positioned responsive to the map. Alternatively or additionally, at the time of implantation of the electrodes, their positions are varied and the results of the variation on hemodynamics are observed, in order to find optimal, fixed positions for the electrodes.
In some preferred embodiments of the present invention, the non-excitatory stimulation pulse is applied between the pacing and the non-excitatory stimulation electrodes. Alternatively, the non-excitatory stimulation pulse may be applied between the. non-excitatory stimulation electrode and the signal generation circuitry case or across a bipolar non-excitatory stimulation electrode.
In some preferred embodiments of the present invention, the extent of change in cardiac output is controlled by changing the characteristics of the non-excitatory stimulation pulse. This is achieved by changing the strength of the electrical signal applied to the heart, i.e., the pulse voltage or current, the pulse timing, the pulse duration and the pulse waveform and frequency thereof, as described in the ""012 PCT application, mentioned above. In particular, the inventors have found that the shape of the non-excitatory signal can determine the magnitude of an increase or decrease in cardiac output.
In alternative preferred embodiments of the present invention, the COEP device may further include one or more physiological sensors, such as, for example, blood flow rate detectors, ventricular pressure detectors, etc., in order to assess cardiac output and to adjust its regulation as needed. Such adjustment may be performed internally, by the signal generation circuitry itself. Alternatively, an external telemetry unit may monitor physiological parameters related to the operation of the COEP device, and may then reprogram the device in response to the values of the parameters.
Further aspects of the present invention are also described in the above-mentioned PCT patent application entitled xe2x80x9cCardiac Output Controller,xe2x80x9d filed on even date and incorporated herein by reference. Other aspects of the use of the COEP device are described further in a PCT patent application PCT/IL97/00231 entitled, xe2x80x9cApparatus and Method for Controlling, the Contractility of Muscles,xe2x80x9d filed on even date, which is assigned to the assignee of the present patent application, and whose disclosure is incorporated herein by reference.
Preferred embodiments of the present invention may also be used in conjunction with suitable drugs, as described in a PCT parent application PCT/IL97/00232 entitled xe2x80x9cDrug-Device Combination for Controlling, the Contractility of Musclesxe2x80x9d, and in conjunction with devices and methods for preventing cardiac fibrillation, as described in a PCT patent application PCT/IL97/00233 entitled xe2x80x9cFencing of Cardiac Musclesxe2x80x9d, both filed on even date and assigned to the assignee of the present application. The disclosures of these applications are also incorporated herein by reference.
There is therefore provided, in accordance with a preferred embodiment of the present invention, apparatus for heart pacing with cardiac output modification, including:
one or more electrodes, which apply electrical signals to cardiac muscle segments; and
signal generation circuitry, which applies an excitatory electrical pulse to at least one of the one or more electrodes to pace the heart and a non-excitatory stimulation pulse to at least one of the one or more electrodes to modify the cardiac output.
Preferably, the circuitry synchronizes the non-excitatory stimulation pulse with the pacing pulse, most preferably by introducing a predetermined time offset between the pacing pulse and the non-excitatory stimulation pulse. In a preferred embodiment of the invention, the circuitry generates a sequence of multiple non-excitatory stimulation pulses, at predetermined respective delays relative to the pacing, pulse.
Preferably, the one or more electrodes include a bipolar non-excitatory stimulation electrode, across which the non-excitatory stimulation pulse is applied.
Additionally or alternatively, the one or more electrodes include a pacing electrode and a non-excitatory stimulation electrode, and the non-excitatory stimulation pulse is applied between the non-excitatory stimulation electrode and the pacing electrode.
Preferably, the signal generation circuitry is encased in an implantable case, and the non-excitatory stimulation pulse is preferably applied between one of the one or more electrodes and the implantable case.
In a preferred embodiment of the invention, the apparatus includes at least one sensor, which senses cardiac activity, preferably an electrode, which senses cardiac electrical activity. The sensor is coupled to the signal generation circuitry, which generates the pulses responsive thereto. Preferably, the signal generation circuitry interrupts application of the excitatory pulse, while generating the non-excitatory pulse responsive to the sensor. Additionally or alternatively, the circuitry detects a QT interval in the cardiac electrical activity.
Further additionally or alternatively, the sensor includes a pressure sensor and/or a flow rate sensor and/or an oxygen sensor and/or a temperature sensor.
Preferably, the signal generation circuitry varies one or more parameters of the non-excitatory stimulation pulse, from the group of parameters including voltage, current, duration, timing delay, waveform and waveform frequency.
Additionally or alternatively, after the non-excitatory stimulation pulse, the signal generation circuitry generates another pulse of opposite polarity to the stimulation pulse, which is applied to the cardiac muscle segment by the non-excitatory stimulation electrode.
Preferably, the one or more electrodes include at least one non-excitatory stimulation electrode having an area of at least 5 mm2, more preferably at least 1 cm2, and most preferably at least 4 cm2.
In a preferred embodiment of the invention, the at least one non-excitatory stimulation electrode includes a net of addressable electrodes. In a further preferred embodiment, the signal generation circuitry varies the extent of a portion of the area of the heart segment to which the non-excitatory stimulation pulse is applied.
In another preferred embodiment of the invention, the apparatus includes a telemetry unit, which receives data indicative of cardiac function and programs the signal generation circuitry to adjust the pulses responsive to the data.
Preferably, application of the non-excitatory stimulation pulse engenders an increase in the cardiac output or, alternatively, a decrease in the cardiac output. Additionally or alternatively, application of the non-excitatory stimulation pulse increases an efficiency of cardiac contraction.
There is further provided, in accordance with a preferred embodiment of the present invention, a method for heart pacing with modification of cardiac contraction, including:
applying one or more electrodes to a subject""s heart;
conveying an excitatory electrical pulse to at least one of the one or more electrodes to pace the heart; and
conveying a non-excitatory stimulation pulse to at least one of the one or more electrodes to modify an efficacy of cardiac contraction.
Preferably, conveying the non-excitatory stimulation pulse includes synchronizing the pulse with the excitatory pacing pulse, preferably by controlling a time offset of the pulse relative to the pacing pulse.
In a preferred embodiment of the invention, conveying the excitatory and non-excitatory pulses includes conveying the pulses to a common one of the one or more electrodes.
Preferably, applying the one or more electrodes includes implanting a pacing electrodes in a first chamber of the heart and implanting a non-excitatory stimulation electrode in another chamber.
Alternatively or additionally, applying the one or more electrodes includes implanting a plurality of electrodes in a single chamber of the heart, and/or implanting at least one non-excitatory stimulation electrodes in each of a plurality of chambers of the heart.
Further alternatively or additionally, applying the one or more electrodes includes fixing an electrode to the epicardium.
In a preferred embodiment of the invention, the method includes applying at least one sensor to the subject""s body, which senses cardiac activity, and conveying the non-excitatory stimulation pulse includes generating a pulse responsive to the activity.
Preferably, applying the at least one sensor includes implanting at least one sensing electrode in the heart. Further preferably, generating the pulse includes detecting a QT interval in an electrical signal received by the sensing electrode and generating a pulse responsive thereto. Preferably, the method includes interrupting the conveyance of the excitatory pulse while conveying the non-excitatory pulse responsive to the activity.
Additionally or alternatively, applying the at least one sensor includes applying a body surface electrode to the subject.
Further additionally or alternatively, applying the at least one sensor includes applying a flow sensor and/or a pressure sensor and/or an oxygen sensor and/or a temperature sensor.
In a preferred embodiment of the invention, generating the pulse includes receiving signals from the sensor via telemetry, and varying a parameter of the pulse responsive thereto.
Preferably, applying the electrodes includes applying electrodes so as to convey the non-excitatory pulse to a segment of the heart having an area of at least 5 mm2, more preferably at least 1 cm2, and most preferably at least 4 cm2.
In a preferred embodiment of the invention, conveying the non-excitatory pulse includes varying an area of the heart to which non-excitatory pulses are applied.
Preferably, conveying the non-excitatory pulse includes varying one or more parameters of the pulse from the group of parameters including voltage, current, duration, timing delay, waveform and waveform frequency.
Further preferably, after conveying the non-excitatory pulse to the at least one of the one or more electrodes, another pulse of opposite polarity thereto is conveyed to the electrodes.
Preferably, modifying the efficacy includes increasing the cardiac output, or alternatively, decreasing the cardiac output. Additionally or alternatively, modifying the efficacy includes enhancing the efficiency of cardiac contraction.
The present invention will be more filly understood from the following detailed description of the preferred embodiments thereof, taken together with the drawings in which: